Uses of Saxenda 6mg/ml Injection
Indications
Saxenda® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults with a baseline Body Mass Index (BMI) of:

≥ 30 kg/m2 (obese).

Or ≥ 27 kg/m2 to < 30 kg/m2 (overweight) and at least one weight-related condition such as dysglycemia (prediabetes or type 2 diabetes), hypertension, dyslipidemia or obstructive sleep apnea.

Saxenda® treatment should be discontinued after 12 weeks at a dose of 3.0 mg/day if the patient has not lost at least 5% of their initial body weight.

Pharmacodynamics
Pharmacotherapeutic group: Drugs used in diabetes, glucagon-like peptide-1 (GLP-1) analogues.

ATC code: A10BJ02.

Mechanism of action

Liraglutide is an acyl-linked human glucagon-like peptide-1 (GLP-1) analogue with 97% amino acid sequence identity to endogenous human GLP-1. Liraglutide binds to and activates the GLP-1 receptor.

GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not fully understood. In animal studies, peripheral injection of liraglutide acts on specific brain regions involved in appetite regulation, where liraglutide, through specific activation of the GLP-1 receptor, increases satiety and reduces hunger signals, thereby reducing body weight.

Pharmacodynamic effects

Liraglutide reduces human body weight primarily through reductions in fat mass, with a greater reduction in visceral fat than subcutaneous fat. Liraglutide regulates appetite by increasing satiety and anorexia, while reducing hunger and subsequent food digestion, thereby reducing food intake.

Liraglutide did not increase energy expenditure compared to placebo.

Liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner, thereby reducing both fasting and postprandial glucose. The glucose-lowering effect is more pronounced in prediabetic and diabetic patients than in normoglycemic subjects. Clinical trials have shown that liraglutide improves and maintains beta-cell function, as indicated by HOMA-B, and the proinsulin to insulin ratio.

Clinical efficacy and safety

The efficacy and safety of liraglutide in weight management in combination with a reduced-calorie diet and increased physical activity were studied in four randomized, double-blind, placebo-controlled phase 3 trials involving a total of 5,358 patients. Refer to the results of 4 experiments in the package insert.

Pharmacokinetics
Absorption

After subcutaneous injection, liraglutide is absorbed slowly, reaching peak concentrations approximately 11 hours after administration. The mean steady-state concentration of liraglutide (AUC 24) was approximately 31 nmol/l in obese patients (BMI 30-40 kg/m3) after 3 mg liraglutide.

Liraglutide exposure increased proportionally to the dose. The absolute bioavailability of liraglutide after subcutaneous injection was approximately 55%.

Distribution

The mean apparent volume of distribution after subcutaneous injection was 20-25 l (for a person weighing approximately 100 kg).

Liraglutide is highly bound to plasma proteins (> 98%).

Biotransformation

During the 24-hour period following a single dose of [H]-labeled liraglutide in healthy subjects, the major circulating component in plasma was intact liraglutide. Two minor plasma metabolites were detected (<9% and 55% of total plasma radioactivity exposure).

Excretion

Liraglutide is endogenously metabolized in a manner similar to macromolecular proteins without a specific major excretory organ. Following a single dose of (H)-liraglutide, no intact liraglutide was detected in urine or feces. Only a small fraction of the administered radioactivity was eliminated as liraglutide-conjugated metabolites in urine or feces (6% and 5%, respectively). The radioactivity in urine and feces was eliminated primarily during the first 6–8 days, and corresponded to three minor metabolites.

Median clearance after subcutaneous administration of liraglutide is approximately 0.9-1.4 L/h with a half-life of approximately 13 hours.

Special patient populations

Elderly: Age did not have a clinically relevant effect on the pharmacokinetics of liraglutide, based on results of population pharmacokinetic analyses of overweight and obese patients (18-82 years of age). No dosage adjustment is required based on age.

Gender: Based on results of population pharmacokinetic analyses, women had a 24% lower body weight-adjusted clearance of liraglutide compared to men. Based on exposure response data, no dosage adjustment is required based on gender.

Race: Ethnic origin had no clinically meaningful effect on the pharmacokinetics of liraglutide, based on results of a population pharmacokinetic analysis, which included overweight and obese white, black, Asian, and Hispanic/non-Hispanic patients.

Body weight: Liraglutide exposure decreased with increasing body weight.

Note

Before using the drug, you need to read the instructions for use carefully and refer to the information below.

Contraindications
Saxenda® is contraindicated in the following cases:

Hypersensitivity to liraglutide or to any of the excipients in the list of excipients.
Precautions for use
This drug is only used with a doctor's prescription.

In diabetic patients, do not use liraglutide to replace insulin.

There is currently limited experience in patients with congestive heart failure of class I-II according to the classification of the New York Heart Association (NYHA). Therefore, caution should be exercised when using liraglutide. There is no experience in patients with class III-IV heart failure according to the classification of the New York Heart Association (NYHA), so liraglutide is not recommended for these patients.

The safety and efficacy of liraglutide in weight management have not been established in the following patients:

Over 75 years of age.
Treated with other weight management agents,
Patients with obesity secondary to endocrine disorders or eating disorders, or those receiving pharmacological treatments that may cause weight gain.
Severe renal impairment.
Severe hepatic impairment.
The use of liraglutide in these patients is not recommended (see Dosage and Administration).

The effect of liraglutide on weight management has not been studied in patients with mild or moderate hepatic impairment and therefore should be used with caution in these patients (see Dosage and Administration, Pharmacokinetic properties).

Experience is limited in patients with enterocolitis and gastroparesis associated with diabetes. The use of liraglutide is not recommended in these patients due to transient gastrointestinal side effects, including nausea, vomiting and diarrhoea.

Pancreatitis

The use of GLP-1 receptor agonists is associated with an increased risk of developing acute pancreatitis. There have been a few reports of acute pancreatitis with liraglutide. If pancreatitis is suspected, liraglutide should be discontinued; if acute pancreatitis is confirmed, liraglutide should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

Gallstones and cholecystitis

In clinical trials of weight management, there was a higher incidence of gallstones and cholecystitis in patients treated with liraglutide compared to patients treated with placebo. The fact that significant weight loss may increase the risk of gallstones is therefore only partly explained by the higher incidence of cholecystitis. Gallstones and cholecystitis may require hospitalization and cholecystectomy. Patients should be informed of the characteristic symptoms of gallstones and cholecystitis.

Thyroid disease

In clinical trials of type 2 diabetes, adverse effects on the thyroid, including hypercalcitonemia, goiter, and thyroid cancer, have been reported, especially in patients with pre-existing thyroid disease. Some cases of hypercalcitonemia have also been observed in weight management clinical trials. Therefore, liraglutide should be used with caution in patients with thyroid disease.

Heart rate

Increases in heart rate have been observed with liraglutide in clinical trials (see section Pharmacokinetic properties). The clinical significance of increases in heart rate during liraglutide treatment is unclear, especially in patients with underlying cardiac or cerebrovascular disease, due to limited data from clinical trials. Heart rate should be monitored regularly in accordance with routine clinical practice. Patients should be informed of symptoms of increased heart rate (palpitations or a feeling of rapid heartbeat at rest). In patients with clinically significant increases in heart rate at rest, liraglutide treatment should be discontinued.

Dehydration

Signs and symptoms of dehydration, including renal failure and acute renal failure, have been reported in patients treated with GLP-1 receptor agonists. Patients treated with liraglutide should be counseled about the potential risk of dehydration associated with gastrointestinal side effects and precautions should be taken to avoid dehydration.

Hypoglycemia in patients with type 2 diabetes

Patients with type 2 diabetes treated with liraglutide in combination with a sulfonylurea may be at increased risk of hypoglycemia. The risk of hypoglycemia may be reduced by reducing the dose of the sulfonylurea. The addition of Saxenda® to patients on insulin has not been evaluated.

Use in pregnancy and lactation

Potential for pregnancy

There are insufficient data from the use of liraglutide in pregnant women. Studies in animals have shown reproductive toxicity (see Preclinical safety data). The potential risk to humans is unknown.

Liraglutide should not be used during pregnancy. If the patient wishes to become pregnant, or if pregnancy is detected while taking the drug, liraglutide treatment should be discontinued.

Breastfeeding

It is not known whether liraglutide is excreted in human milk. Animal studies have shown that transfer of liraglutide and its structurally related metabolites into milk is low. Preclinical studies have shown a treatment-related reduction in growth in breastfed newborn rats. Due to lack of experience, 20 Saxenda® should not be used in

Storage

Special precautions for storage.

Store in the refrigerator (2°C - 8°C). Do not freeze.

Keep away from the freezer.

After first use: Store below 30°C or in the refrigerator (2°C - 8°C). The product should be discarded 1 month after first use.

Keep the pen cap closed to protect from light.